10 PRINCIPLES OF ORGANIC MEDICINAL CHEMISTRY activation of the G-proteins a variety biochemical signal transduction pathways can be acti. vated.Many chemical messengers,like hormones and various neurotransmitters,act through G-protein coupled receptors.They are also known as metabotropic receptors or 7- transmembrane receptors.Ex:Muscarinic acetylcholine receptors and adrenergic receptors. (iii)Tyrosine Kinase-linked Receptors.Tyrosine kinase-linked receptors.are mem brane bound ceptors and contain an intrinsic enz matic function (tyrosine kinase activity) in their intracellular domain.Upon combination with ligand like insulin,the receptor is acti- vated and is able to phosphorylate tyrosine residues of other intracellular proteins.Protein phosphorylation is one of the underlying mechanisms of the regulation of protein function.Ex: Receptors for insulin and various cytokines and growth factors. Kinase-linked G-protein coupled receptors Intracellular steroid receptor C -N DNA binding Sch representation of the four majo for the are localised in the cell membrane.The ligand-gated on channels are made up of an assembly by 4-5 subunits,which each contain four transmembrane domains ()gene transeription:Intracellular receptor regulating gene transcription.which are located in the binding of the a nr ate chemical e.g.steroid hormones.the activated receptors translate to the nucleus and initi ate gene transcription.These are also known as nuclear receptors.Ex:Receptors for steroid hormones,thyroid hormones and vitamin D. Drug Receptor Interactions duce ph ee-point 10 PRINCIPLES OF ORGANIC MEDICINAL CHEMISTRY C-8—N-CHEMI\CHE2-1.PM5 activation of the G-proteins a variety biochemical signal transduction pathways can be acti￾vated. Many chemical messengers, like hormones and various neurotransmitters, act through G-protein coupled receptors. They are also known as metabotropic receptors or 7- transmembrane receptors. Ex: Muscarinic acetylcholine receptors and adrenergic receptors. (iii) Tyrosine Kinase-linked Receptors. Tyrosine kinase-linked receptors, are mem￾brane bound receptors and contain an intrinsic enzymatic function (tyrosine kinase activity) in their intracellular domain. Upon combination with ligand like insulin, the receptor is acti￾vated and is able to phosphorylate tyrosine residues of other intracellular proteins. Protein phosphorylation is one of the underlying mechanisms of the regulation of protein function. Ex: Receptors for insulin and various cytokines and growth factors. N N Kinase-linked receptors G-protein coupled receptors Ligand-gated Ion-channels N C C C 4X tyrosine kinase Intracellular steroid receptor ligand binding DNA binding C N Schematic representation of the four major classes of receptor proteins. Except for the steroid receptors, the receptor proteins are localised in the cell membrane. The ligand-gated ion channels are made up of an assembly by 4–5 subunits, which each contain four transmembrane domains. (iv) Intracellular receptors regulating gene transcription: Intracellular receptors regulating gene transcription, which are located in the cytosol. Upon binding of the appropri￾ate chemical e.g. steroid hormones, the activated receptors translate to the nucleus and initi￾ate gene transcription. These are also known as nuclear receptors. Ex: Receptors for steroid hormones, thyroid hormones and vitamin D. Drug Receptor Interactions Majority of drugs show remarkably high correlation of structure and specificity to pro￾duce pharmacological effects. A minimum three-point attachment of a drug to a receptor site is